Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg...

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Autores principales:	Maria C Whelan, Garrett Casey, John O Larkin, Barbara-ann Guinn, Gerald C O'Sullivan, Mark Tangney
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fb9eb08e7824095812a83065933474d
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spelling	oai:doaj.org-article:6fb9eb08e7824095812a83065933474d2021-11-18T08:19:02ZOral tolerance to cancer can be abrogated by T regulatory cell inhibition.1932-620310.1371/journal.pone.0097602https://doaj.org/article/6fb9eb08e7824095812a83065933474d2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24832130/?tool=EBIhttps://doaj.org/toc/1932-6203Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue--JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups--this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut.Maria C WhelanGarrett CaseyJohn O LarkinBarbara-ann GuinnGerald C O'SullivanMark TangneyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97602 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria C Whelan Garrett Casey John O Larkin Barbara-ann Guinn Gerald C O'Sullivan Mark Tangney Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.
description	Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue--JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups--this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut.
format	article
author	Maria C Whelan Garrett Casey John O Larkin Barbara-ann Guinn Gerald C O'Sullivan Mark Tangney
author_facet	Maria C Whelan Garrett Casey John O Larkin Barbara-ann Guinn Gerald C O'Sullivan Mark Tangney
author_sort	Maria C Whelan
title	Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.
title_short	Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.
title_full	Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.
title_fullStr	Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.
title_full_unstemmed	Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.
title_sort	oral tolerance to cancer can be abrogated by t regulatory cell inhibition.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6fb9eb08e7824095812a83065933474d
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_version_	1718421928518090752

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.

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